Antibiotic Resistance

Antibiotic Resistance and the Terrifying Possibility

Medical problems are worsening as pathogens mutate. Now is the time to take drug resistance seriously.

Most of us never imagined that gardening could be dangerous. It may sound strange, but on March 14, 1941, a British policeman named Albert Alexander died for this very reason. The story goes like this: The policeman's face was scratched by a rose in the garden. The wound became infected by a group of bacteria. Sepsis (blood poisoning) spread throughout his body. He lost his eye, and then his life.

His treatment was almost complete, but Alexander's luck ran out. The extract, created from the mold/fungus, was repeatedly injected into Alexander's body, and the microbe was almost completely eradicated. However, before all the bacteria were dead, the scientists ran out of medication. Therefore, the treatment was left incomplete, and the blood poisoning returned.

Like other bacteria-killing antibiotics, penicillin is widely used today. A thorn scratch is normally not a potential killer, but rather a simple irritant. However, we shouldn't be too optimistic about this. A study by the US Centers for Disease Control and Prevention (CDC) showed that between 2000 and 2008, cases of blood poisoning increased from 621,000 to 1,141,000, and related deaths increased from 154,000 to 207,000. One reason for this is the emergence of Methicillin-Resistant Staphylococcus aureus, which cannot be killed by methicillin, one of the most effective types of penicillin. This is a small harbinger of what is to come. Three years ago, the CDC compiled a list of 18 antibiotic-resistant microbes threatening American health. Five of these, including MRSA, cause blood poisoning.

When people hear about antibiotic-resistant bacteria, they often perceive it as a new, uncontrollable disease or epidemic. While the real threat may not seem obvious, the existing problems are actually becoming increasingly complex. Hospital-acquired infections are a prime example. The rise of antibiotic resistance is making hospital-acquired infections an intractable problem. Even seemingly simple surgical procedures like hip replacement surgery can become very risky because of this. The same can be true for cesarean births. Antibiotic resistance can also increase the risk in procedures that suppress the immune system, such as organ transplants and cancer chemotherapy.

This situation may not be limited to hospitals. In particularly impoverished countries, drug-resistant tuberculosis strains cause 200,000 deaths annually. Most of those who die from tuberculosis today do not die from the aforementioned strains. However, these strains are responsible for more than eight of the fatal cases that would normally respond to treatment.

Gonococcus (gonorrhea microbe) Gonococcus is another microbe that develops persistent antibiotic resistance. When penicillin was first discovered, it was quite effective in fighting gonococcus. As the effectiveness of penicillin decreased, tetracyclines began to be used in its place, and although combinations of several other substances began to be used against gonococcus, these substances remained quite limited.

Microbial resistance to drugs is not limited to antibiotics. The same is true, especially in impoverished countries, for drugs used to treat parasites like malaria and viruses like HIV. Resistance to drugs that kill the parasite in malaria has been a problem the medical world has been trying to solve for decades. Since the beginning of the century, the use of the new drug artemisinin has given scientists some relief. However, artemisinin-resistant parasites have emerged today. The same is true for drug combinations used against the HIV virus since the 1990s. This type of drug resistance can only be overcome by using other drugs. However, this also carries the risk of worsening the treatment.

The root of the problem goes back quite a long time. Alexander Fleming, who discovered the effects of penicillin, warned about the dangers of drug resistance when the drug was launched as a major success. The fact that these warnings are in the past doesn't mean they are irrelevant or that the situation won't get worse. A study led by Jim O'Neill, working for the British Government and the Wellcome Trust, shares the latest findings on antimicrobial drug resistance. According to Mr. O'Neill and his colleagues, 700,000 people die each year from infections caused by drug-resistant pathogens and parasites. If this continues, scientists believe this could reach 10 million by 2050, wiping out 2% to 3,5% of global GDP. Currently, the American healthcare system spends $20 billion annually on infections resistant to one or more antibiotics.

Ongoing Change

Drug resistance is a simple but often misunderstood phenomenon. Antibiotics kill bacteria mostly by inhibiting the synthesis of new proteins or the construction of cell walls. Any change in the bacterial genome reduces the effectiveness of these drugs while allowing the bacterial population to increase. This genetic alteration can change the physiology of microbes by increasing the production of proteins that rid them of harmful molecules. This can lead to the production of an enzyme that negates the drug's effect, or it can alter the shape of the molecule, making it less of a target for the drug.

Humans are certainly not the first beings on Earth to seek to kill microbes. For example, fungi produce penicillin to protect themselves against some bacteria. A large portion of the 20 types of antibiotics used medically are derived from these natural germicides. However, this does not mean that existing microbes are not facing entirely new threats. Bacterial populations generally possess resistance genes, programmed to remain hidden when threatened, waiting for the opportune moment to emerge.

When these genes emerge, they can quickly spread to other bacteria. Bacteria store some of their genes in small, easily transmissible DNA strands called plasmids. Think of them like programs on a USB stick. These plasmids enable the exchange of resistance not only between members of the same population but also between different species. Genes that cause deadly diseases spread in the same way.

Thus, the genes necessary for resistance can be easily obtained. Like other biological traits, resistance does not develop spontaneously. The production of bacterial evacuation pumps or specific drug-degrading enzymes requires energy and material expenditure from the microorganism. Therefore, altering the shape of molecules makes them resistant to the drug while causing them to work less than before. Copying the DNA of the resistance gene imposes a metabolic burden. Furthermore, the fact that different antibiotics require different resistance genes means that a microbe needs to be used more frequently, increasing costs. Therefore, resistance tends to remain at its highest level when these drugs are available. This leads us to the conclusion that if bacteria are exposed to fewer drugs, resistance will decrease proportionally.

At this point, it would be useful to address the misconception mentioned above. There is a common perception that it is not the microbes but the people taking the medication who develop resistance to its effects. According to last year's World Health Organization research, this is the perception among people in low- and middle-income countries. A 2015 Wellcome Trust survey indicated a similar misconception exists in the UK as well.

This misconception certainly has consequences. If you are aware that the bacteria have developed resistance, medication may still be somewhat effective. It's worth remembering: don't use medication unless necessary. When you do use it, make sure it kills all the bacteria. However, if you fall into the misconception that people have developed resistance, you won't hesitate to use antibiotics. And when you see your illness improve slightly, you will most likely stop taking the antibiotics instead of continuing until you are completely cured. And if you have used antibiotics without a prescription, even worse consequences await you.

Mr. O'Neill believes that public awareness campaigns on this issue would be beneficial. The fact that medications are prescribed by specialists does not mean there will be no problems. In the US, an average of 40 million patients are prescribed antibiotics each year for respiratory problems. Antimicrobial Chemotherapy (Journal of Antimicrobial ChemotherapyAccording to an article in the journal, it is estimated that in 2013, two-thirds of patients used antibiotics even though they did not need them.

Some situations can be more interesting. For example, a patient with viral pharyngitis wants to see concrete evidence when they go to the doctor, even though antibiotics are unlikely to work. Sometimes, the opposite is true. Prescribing antibiotics might be effective when the doctor can't pinpoint the exact cause of the illness. In such cases, the chance of curing a patient might outweigh the threat of developing bacterial resistance.

Know your enemy.

One way to reduce the development of resistance is through comprehensive detection of bacterial infections. For this, diagnostic kits can be incredibly fast and inexpensive, surpassing even preventative antibiotics. Identifying which antibiotics an infection is susceptible to increases the value of the diagnostic kit. For example, if gonorrhea can be successfully treated with penicillin, expensive antibiotics will not be prescribed; this would be beneficial both financially and in terms of overall public health.

Antibiotic resistance doesn't only develop and spread in medical settings. In many places, antibiotics are given to animals more than to humans. For example, in America, 70% of antibiotics are sold for livestock and poultry. While some are for therapeutic purposes, most are sold for other purposes. Although the underlying reasons are not fully understood, animals fed these drugs gain weight faster. Bacteria that develop resistance are unlikely to become human pathogens. However, these resistance genes can easily be transferred to other microbes.

Some of the antibiotics used by farmers are medications that doctors keep for worst-case scenarios. Although colistin is not widely used in humans because it can damage the kidneys, this antibiotic is quite effective in fighting many types of bacteria. Last year, bacteria carrying colistin-resistant genes (plasmids) were found among patients in a hospital in China. This is thought to be due to the agricultural use of colistin.

The cost of banning antibiotics used to promote growth would not be high. Research by the US government has shown that such a ban would reduce antibiotic use by less than 1%. The European Union already implements this ban. Despite the challenges in implementation, the choice between growth-promoting doses and prophylaxis (preventive health) given under veterinary control is entirely up to the user.

Mr. O'Neill supports such bans. He also advocates for more vaccinations to reduce the need for treatment in both humans and farm animals. Another focus is hospital hygiene. In cases similar to Albert Alexander's death, hospital staff are known to not pay much attention to cleanliness.

One approach to making existing antibiotics more effective is to produce more similar drugs or functionally equivalent alternatives. With the introduction of penicillin, pharmaceutical companies raced to produce new antibiotic molecules. However, this interest has gradually waned. New products in different stages of clinical trials show efficacy in only about 40% of cases. Of these drugs, each representing a significant investment, only a small fraction are released to the market.

There are specific reasons why pharmaceutical companies do not invest in antibiotic production. These companies prefer chronic rather than acute illnesses, investing in drugs that patients will use for a long time. Furthermore, despite the increasing problem of antibiotic resistance, existing antibiotics are often effective in treatment, and new drugs do not cover their production costs. Established drugs are relatively cheaper because they are not patent-protected. Considering the potential for drug resistance, public policy will not support the use of new drugs, negatively impacting sales.

Since microbes will develop less resistance to drugs they have forgotten, a reasonable portion of the resulting shortage could be covered by reintroducing unused drugs to the market. Another option could be to replenish antibiotics categorized as emergency supplies. According to O'Neill's report, one-time payments ranging from $800 million to $1,3 billion will be made to companies producing drugs that are expected to meet the shortage, based on revenue from sales. At this year's World Economic Forum in Davos, 85 companies indicated they would do their best if governments met certain conditions and provided the necessary funding.

The problem mentioned above may go beyond incentives. Some believe there may be difficulties in obtaining the raw materials needed for research—that is, molecules that can be transformed into antibiotic drugs. The intense search for raw materials in the mid-20th century may have largely depleted natural resources.

In the late 1990s, established pharmaceutical companies and innovative biotechnology companies conducted detailed research into new drugs, ranging from bacteria to genome sequences. David Payne, a researcher at GlaxoSmithKline, states that his company examined an average of 70 targets in this way. The company aimed to find the key components that would take the research to the next level, building on experience gained in other therapeutic areas. However, the company only managed to achieve six of these targets. Considering the overall attrition involved in the research, it is clear that this effort was wasted.

Although today's advanced genomics science suggests different things, it would be beneficial to examine alternative approaches. One such approach is the use of specially formulated antibodies instead of traditional small-molecule drugs. One advantage of this would be to equip bacteria with weapons they haven't encountered before. It's also important to remember that yeasts and other microbes cannot produce antibodies. However, the high cost of therapeutic antibodies is a disadvantage of this approach.

Another option is viruses that kill bacteria, known as bacteriophages. Just as bacteria produce resistance genes against natural antibiotics, they also protect themselves against bacteriophages. (In fact, CRISPR-Cas9, the newest genome sequencing tool in biotechnology, is based on a system where bacteria break down the genes of viruses that attack them.) Bacteriophages have been used for therapeutic purposes for decades. Therefore, having more detailed information about bacterial genomes means using them more effectively than before.

There are also environmentally conscious approaches to this issue. Beneficial bacteria are found in certain parts of the body, particularly the skin and intestines. Some data suggests that by managing these bacteria, they can be less exposed to external influences. This approach is relevant to the CDC's list of most dangerous bacteria. Clostridium difficile It has been effective against the microbe. Additionally, there are drugs available that can make the patient's immune response more effective.

All these possibilities show that panic is unnecessary. However, there is a strong reason that compels us to act. For example, Florey and Chian were motivated by a crisis. This crisis stemmed from the fact that many of the wounded in World War II died from sepsis (blood poisoning). While the current situation may not be that severe, we are facing a fierce battle requiring action on behavioral, economic, and medical fronts. Ultimately, war is war in all its forms, and the most effective method of combating it must be found.

*This text is a translation of an article from The Economist dated May 21, 2016. Habit Gıda AŞ bears no responsibility for the content of this article. This article is for informational purposes only, has been translated from English to Turkish, and does not contain any health advice. Habit Gıda AŞ cannot be held responsible for any health problems that may arise in readers as a result of this article. Readers should not take any action based on the content of this article without consulting their doctor regarding their health condition. You should consult your doctor about all matters related to your health.

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